Anti-IL-17A antibody and use thereof
The present invention provides an antibody or a functional fragment thereof that specifically binds to IL-17A with high affinity. Also provided are a nucleic acid molecule encoding the antibody or the functional fragment thereof disclosed herein, an expression vector and a host cell for expressing the antibody or the functional fragment thereof disclosed herein, and a method for preparing the antibody or the functional fragment thereof disclosed herein. The present invention also provides a pharmaceutical composition comprising the antibody or the functional fragment thereof disclosed herein, and use of the antibody or the functional fragment thereof disclosed herein for treating an immune dysfunction disease.
1. An antibody or an antigen-binding fragment thereof that specifically binds to IL-17A, comprising a heavy chain variable region (VH) comprising HCDR1, HCDR2 and HCDR3; and a light chain variable region (VL) comprising LCDR1, LCDR2 and LCDR3; wherein
amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 comprise SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 comprise SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15, respectively; or
amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 comprise SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 comprises SEQ ID NO: 16, SEQ ID NO: 17 and SEQ ID NO: 18, respectively; or
amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 comprise SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively, and amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 comprise SEQ ID NO: 19, SEQ ID NO: 20 and SEQ ID NO: 21, respectively; or
amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 comprise SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively, and amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 comprise SEQ ID NO: 22, SEQ ID NO: 23 and SEQ ID NO: 24, respectively; or
amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 comprise SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, respectively, and amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 comprise SEQ ID NO: 22, SEQ ID NO: 23 and SEQ ID NO: 24, respectively; or
amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 comprise SEQ ID NO: 60, SEQ ID NO: 61 and SEQ ID NO: 62, respectively, and amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 comprise SEQ ID NO: 63, SEQ ID NO: 64 and SEQ ID NO: 65, respectively.
2. The antibody or the antigen-binding fragment thereof according to claim 1 comprising a heavy chain variable region (VH) having an amino acid sequence selected from SEQ ID NOs: 25, 26, 27, 28, 33, 35, 37 and 40, and a light chain variable region (VL) having an amino acid sequence selected from SEQ ID NOs: 29, 30, 31, 32, 34, 36, 38, 39 and 41.
3. The antibody or the antigen-binding fragment thereof according to claim 1 , wherein
the heavy chain variable region comprises SEQ ID NO: 25, and the light chain variable region comprises SEQ ID NO: 29 or 30; or
the heavy chain variable region comprises SEQ ID NO: 26, and the light chain variable region comprises SEQ ID NO: 31; or
the heavy chain variable region comprises SEQ ID NO: 27 or 28, and the light chain variable region comprises SEQ ID NO: 32; or
the heavy chain variable region comprises SEQ ID NO: 33 or 35, and the light chain variable region comprises SEQ ID NO: 34; or
the heavy chain variable region comprises SEQ ID NO: 35, and the light chain variable region comprises SEQ ID NO: 36; or
the heavy chain variable region comprises SEQ ID NO: 37, and the light chain variable region comprises SEQ ID NO: 38 or 39; or
the heavy chain variable region comprises SEQ ID NO: 40, and the light chain variable region comprises SEQ ID NO: 41.
4. The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody or the antigen-binding fragment thereof is a murine antibody, a chimeric antibody, or a humanized antibody.
5. The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody is an intact antibody and the antigen-binding fragment is selected from a single chain antibody, an Fab antibody, an Fab′ antibody, an (Fab′) 2 antibody, a bispecific antibody and a multispecific antibody.
6. The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody or the antigen-binding fragment thereof is of an IgG1, IgG2, IgG3 or IgG4 type.
7. The antibody or the antigen-binding fragment thereof according to claim 1 , comprising a heavy chain (HC) having an amino acid sequence selected from SEQ ID NOs: 42, 44, 46 and 49, and a light chain (LC) having an amino acid sequence selected from SEQ ID NOs: 43, 45, 47, 48 and 50.
8. The antibody or the antigen-binding fragment thereof according to claim 7 , wherein
the light chain has an amino acid sequence set forth in SEQ ID No: 43 and the heavy chain has an amino acid sequence set forth in SEQ ID No: 42 or 44; or
the light chain has an amino acid sequence set forth in SEQ ID No: 45 and the heavy chain has an amino acid sequence set forth in SEQ ID No: 44; or
the light chain has an amino acid sequence set forth in SEQ ID No: 47 or 48 and the heavy chain has an amino acid sequence set forth in SEQ ID No: 46; or
the light chain has an amino acid sequence set forth in SEQ ID No: 50 and the heavy chain has an amino acid sequence set forth in SEQ ID No: 49.
9. An isolated nucleic acid molecule or isolated nucleic acid molecules encoding the antibody or the antigen-binding fragment thereof according to claim 1 .
10. The isolated nucleic acid molecule or the isolated nucleic acid molecules of claim 9 , wherein the isolated nucleic acid molecules are selected from the group consisting of SEQ ID NOs: 51 and 52, SEQ ID NOs: 53 and 52, SEQ ID NOs: 53 and 54, SEQ ID NOs: 55 and 56, SEQ ID NOs: 55 and 57, and SEQ ID NOs: 58 and 59.
11. An expression vector or a recombinant vector comprising the isolated nucleic acid molecule or the isolated nucleic acid molecules according to claim 9 .
12. A host cell transformed with the expression vector or the recombinant vector according to claim 11 .
13. A pharmaceutical composition, comprising
(i) the antibody or the antigen-binding fragment thereof according to claim 1 , a nucleic acid molecule or nucleic acid molecules encoding the antibody or the antigen-binding fragment thereof, a vector comprising the nucleic acid molecule or the nucleic acid molecules; or
(ii) a host cell comprising the nucleic acid molecule or the nucleic acid molecules or the vector; and
a pharmaceutically acceptable carrier or excipient.
14. A method for preventing or treating a disease or a disorder diseases or disorders mediated by IL-17A, comprising administering to a subject in need of a therapeutically effective amount of
(i) the antibody or the antigen-binding a functional fragment thereof of claim 1 ; or
(ii) a nucleic acid molecule or nucleic acid molecules encoding the antibody or the antigen-binding functional fragment thereof, or a vector comprising the nucleic acid molecule or the nucleic acid molecules; or
(iii) a pharmaceutical composition comprising the antibody or the antigen-binding functional fragment thereof, the nucleic acid molecule or the nucleic acid molecules, or the expression vector.
15. The method of claim 14 , wherein the disease is arthritis, rheumatoid arthritis, psoriasis, ankylosing spondylitis, chronic obstructive pulmonary disease, systemic lupus erythematosus (SLE), lupus nephritis, asthma, multiple sclerosis or cystic fibrosis.